Professor Brent Stockwell

Pronouns: He/Him

Professor of Biological Sciences and of Chemistry, Graduate School of Architecture, Planning, & Preservation

Professor of Chemistry,

Professor of Pathology and Cell Biology,

USA

BIOGRAPHY:

Brent R. Stockwell, PhD, is the William R. Kenan Jr. Professor of Biological Sciences and Chair of the Department of Biological Sciences, Professor of Chemistry, Columbia University, and Professor of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center.

 

His research involves the discovery of small molecules that can be used to understand and treat cancer and neurodegeneration, with a focus on biochemical mechanisms governing cell death. In a series of papers from 2003-2012, Dr. Stockwell discovered a new form of cell death known as ferroptosis. Since then, his lab has defined the major mechanisms governing ferroptosis, its therapeutic implications, and key reagents for studying this new form of cell death.

 

Dr. Stockwell has received numerous awards, including being elected to the National Academy of Medicine, receiving a Burroughs Wellcome Fund Career Award at the Scientific Interface, a Beckman Young Investigator Award, an HHMI Early Career Scientist Award, the BioAccelerate NYC Prize, the Lenfest Distinguished Columbia Faculty Award, the Great Teacher of Columbia College Award from the Society of Columbia Graduates, the Dean Peter Awn Commitment to the LGBTQ community Faculty Award, and an NCI R35 Outstanding Investigator Award. He has been in the top one percent of highly cited researchers the last three years and was named as one of the 50 most influential life science individuals in New York.

 

He has developed a new blended learning approach to teaching biochemistry, performed randomized controlled trials to examine the effectiveness of teaching methods, and introduced the use of virtual reality and augmented and mixed reality into his biochemistry course. He has given more than 150 seminars around the world, trained more than 100 undergraduate and graduate students, technicians and postdoctoral scientists, published >180 scientific articles, been awarded 23 US patents, and received >50 research grants for >$40 million. He founded the biopharmaceutical companies CombinatoRx Incorporated, Inzen Therapeutics, ProJenX, Inc. and Exarta Therapeutics, and is the author of The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines and is a top-ranked writer on Medium.

 

RECENT POSTS FROM STATE OF THE PLANET

Jan 08, 2024

What’s the Difference Between Plant and Animal Protein?

They’re different biochemical languages that profoundly affect health

Image of one hand holding a burger and the other hand holding oatmeal with berries
Image: Adobe Stock

Plants and animals look different, but they both contain a lot of protein. And since protein is one of the most crucial nutrients in the foods you eat, you’re wise to understand what it is, how it works, and which kind is best. Bodybuilders think they need it to build muscle. Vegans worry they don’t get enough of it. Many of us are just baffled by it.

What is protein, and is there any difference in where it comes from? Is eating plant protein and animal protein equivalent?

What we call protein in food is a mixture of thousands of different flavors of protein. These many large molecules are built from repeating units called amino acids — there are 20 common types of such amino acids. Each type of protein has a unique sequence of amino acids strung together, like letters that form words and sentences.

Let’s make a simple analogy: Sentences in English can make very different use of the letters of the alphabet. The sentence “The quick brown fox jumps over the lazy dog” uses every letter once, and efficiently too. “An assassin sins” is a phrase that uses only four different letters. If you ate one, each could have very different effects on your body.

But since you don’t typically eat your words (or at least hope not to) here’s some relevant advice: “Eat food. Not too much. Mostly plants,” from writer Michael Pollan. So, then, what’s the real difference in plant and animal protein when we eat them?

Protein letters have different effects on health

When you eat foods with protein, your stomach digests it into individual amino acids, breaking the protein words down into single letters. The amino acid letters are reused by different parts of the body to build new protein words and sentences.

Some of the amino acids from the protein you eat get converted into energy, or into other molecules your body can use. The specific amino acids in the protein you eat have a dramatic effect on what happens to your body after you eat — how the whole story of your health turns out. So why don’t we eat the protein sources that are best for our health?

“Life expectancy would grow by leaps and bounds if green vegetables smelled as good as bacon,” suggested Doug Larson, newspaper columnist.

Plant and animal proteins use letters differently

The alphabet that is used to write both animal and plant proteins is the same set of 20 amino acids. The amino acids are the different letters. A particular protein can be like the word banana that uses more of the letter A, while another protein might be like the word beekeeper that has a lot Es, and an exotic protein might be built from an unusually large number of Ms, such as mammogram.

Plants and animals build their proteins differently, just as words are built differently in Spanish and English. The proteins from plants and animals contain different amounts of each amino acid letter. Plant proteins tend to have more of the amino acids that benefit health, whereas animal proteins often have more of the amino acids harmful to health. The protein in foods we eat thus have different amino acid compositions, which in turn affect health in positive and negative ways.

But different plants themselves use different proteins. Soy, made from soybeans, uses most of the 20 amino acid letters, whereas corn and rice only use a subset of the amino acid letters in their proteins, even though they function fine as plants. This is impressive — like writing an entire book without using seven letters of the alphabet.

The deadliest letter

So which amino acids are good and which are bad? The most dangerous amino acid seems to be methionine. Mice on a diet high in methionine develop anxiety, and have increased risk of heart disease. Eating foods with less methionine slows aging and promotes health. And yes, plants have less methionine than animals. Pork, chicken, and beef are high in methionine. Fruits, mushrooms, and broccoli are low in methionine. One slice of cured ham has the same methionine content as 1,100 apples.

The bottom line: Plant and animal proteins are built from amino acids, but in different proportions. The way we digest and metabolize these different amino acids affects health. Proteins vary tremendously in size and composition. The littlest are under fifty letters, like this sentence. The longest are more than 34,000 letters, about seven times as many as in this entire story.

There is still a vast amount of science to be unraveled about how different amino acids affect the many aspects of health. Understanding that dietary proteins are not interchangeable is the first step to decoding the precise impact of the protein we eat on our well-being.

More Aha! Moments >>>


What’s the Difference Between Plant and Animal Protein? was originally published in Aha! on Medium, where people are continuing the conversation by highlighting and responding to this story.

Nov 08, 2023

Therapeutic Olive Oil: New Research on Food as Medicine

Olive oil contains a fat molecule that protects against diseases involving iron, suggesting new food-based treatment options

Child looks at olive oil bottles
Image credit: Brent Stockwell

A baby girl died in 1992 when her two-year-old sibling fed her more than 30 glossy red and green tablets. Inside the medicine was the metal iron, deadly when taken in excess. The tablets were intended as a supplement for their mother, but found their way into the children’s hands and mouths. Thousands of children are poisoned with iron through such accidents each year, causing tragic deaths.

Iron can cause severe damage, but is also essential for health — too much or too little iron impairs health. Eating foods that provide sufficient iron but also protect against iron toxicity may be key to preventing iron poisoning, and broadly promoting health and longevity. The longest-lived humans have less iron in their blood, as detected by a technology called mass spectrometry, which involves precisely measuring the abundance of different metals based on their exact mass.

“Food is an important part of a balanced diet, “ said Fran Lebowitz.

Indeed, different foods profoundly alter health. My colleagues and I have been studying how iron causes damage and how some fat molecules protect against iron injury. Olive oil and macadamia nuts are protective foods, our new study shows, but a fat-control gene is key for unlocking the protective effect of these fatty molecules. Our data reveal a new axis through which diet controls health and that the details matter — the right foods balance each other.

Iron can be fatal

Iron is the Goldilocks metal — too little iron causes weakness and tiredness, due to insufficient oxygen delivery to the body, but too much iron causes damage to the stomach and related parts of the body, and even death. Iron damage can occur through inheritance, being passed from parent to child, as in the disease hemochromatosis. This disease, so named because it was thought that the unusual color (-chroma-) in these patients was caused by their blood (hemo-), causing this specific condition (-tosis).

Patients in the intensive care unit of hospitals because of trauma, surgery, or severe infection often have multi-organ failure due to elevated blood levels of iron. The source of increased iron in these critical care patients is not known, but may derive from parts of the body that release iron stores when damaged. Reducing the negative effects of iron in such diseases is a challenge.

There are two existing treatments for iron poisoning — bleeding and chelation. Removing iron by bleeding can help with mild iron overload, as blood is the major reservoir of iron. Patients with sickle cell disease have impaired blood function, and often receive blood transfusions to repair the functioning of their blood. However, the additional iron-rich blood these patients receive, while helpful for correcting sickle cell symptoms, can also cause iron overload. Many of these patients take drugs that can chelate, or attach to, iron and eliminate it from the body; such treatments can cause allergic reactions, eye damage, hearing loss, bone thinning, and stomach problems, as iron is important for normal health. Better ways of treating iron overload are needed.

An olive oil fat protects against iron

Olive oil has a component that can block the toxic effects of iron, as we discovered in our newly reported research, done in collaboration with Marcelo Farina, PhD, at Universidade Federal de Santa Catarina in Brazil, and Antonio Miranda Vizuete, PhD, at Instituto de Biomedicina de Sevilla in Spain. The results were just published in the scientific journal Cell Chemical Biology.

Iron’s essential role and dangerous effects come from its ability to act as a small electrical wire. When humans and animals digest nutrients, they use iron’s role as a wire as part of the process of converting sugar, fat, and protein in food into energy.

But iron has a dark side: It also can short-circuit and damage other parts of the body.

The harmful effects of iron can be prevented by an abundant ingredient in olive oil called oleic acid, our study found. The name oleic acid comes from the Latin oleum, a term for oil, as oleic acid is the most common molecule in olive oil. The acid part of this chemical name refers to the fact that it is acidic, like vinegar and tart fruits. Oleic acid is associated with health and longevity, such as being part of the Mediterranean diet, which involves eating fish, whole grains, and olive oil, along with fruit, nuts and vegetables, all favored over red meat. Olive oil is one of the best sources of oleic acid.

Another great source of oleic acid is oil from macadamia nuts, which are also associated with good health. A recent clinical trial by other researchers showed that macadamia nuts improve heart health.

We found in our research that worms, mice and even human cells given iron suffered severe damage. However, oleic acid prevented this damage. Iron attacked certain fat molecules that are particularly susceptible to injury. Oleic acid was resistant to iron’s effects and was able to substitute for the delicate fats, preventing iron’s toxic effect. While studies on cells, mice, and worms don’t always translate directly into human benefit, we think that given the known benefits of olive oil, it is possible that this oil might be useful for treating iron overload in people.

In addition, iron is involved in driving many diseases, even when it doesn’t accumulate to excess. Common brain, heart, liver, and kidney diseases have been reported to involve toxic effects of iron. These reports suggest that oleic acid might be broadly beneficial on many diseases, not just cases of iron poisoning and iron overload. While this is more speculative, it will likely be a subject of research in the near term.

A gene that determines whether olive oil works

But wait — it is not so easy! We also discovered a key gene that determines whether oleic acid can be protective. Genes compose the instruction manual of people and animals that dictate many aspects of health and disease. We found that one particular gene that controls fat production is critical for the ability of oleic acid to protect against injury. When this gene, named PPARA, was not active, oleic acid was not helpful, as oleic acid couldn’t replace delicate fats without the help of PPARA.

These results show that the right diet could help people with iron poisoning or iron overload. People who consume too much iron may benefit from consumption of olive oil. A Mediterranean diet or just a diet rich in olive oil could blunt the toxic effects of iron. Macadamia nuts would also likely work. While olive oil has other benefits for the broader population, olive oil would particularly benefit these individuals through protection against iron.

However, the beneficial effects of oleic acid do depend on the PPARA gene, so it could be helpful for physicians to check if this gene is active in people who are considering taking olive oil or macadamia nut oil to protect against iron. That would require a new medical test for the activity of the PPARA gene, which is not hard to do, but doesn’t yet exist.

“Iron, at the same time [is] the most useful and the most fatal instrument in the hand of mankind,” as Pliny the Elder said more than 2,000 years ago. Little did he know that the same concept applies to iron and our health. Now we know that iron’s ferocious power can be tamed by oleic acid. Yes, as Fran Lebowitz said, food is important, and balancing the right ingredients is the ticket to health and longevity.


Therapeutic Olive Oil: New Research on Food as Medicine was originally published in Wise & Well on Medium, where people are continuing the conversation by highlighting and responding to this story.

Sep 25, 2023

Mysterious Fats Fuel Disease More Than We Knew, New Research Reveals

New technologies detect thousands of different fats throughout the human body that predict disease and determine health

Healthy couple surrounded by fatty molecules
Image credit: Brent Stockwell

A deadly contaminant stopped thousands of people’s hearts, resulting in their deaths, but nobody knew why. Then, in the 1950s, biochemist Fred Kummerow scraped open their arteries and found a lethal fat that had come from their food. As he learned, different fats in our diet are the determinants of health and disease, and control who lives and who doesn’t.

“It’s simple, if it jiggles, it’s fat,” Arnold Schwarzenegger once said. How wrong he was. Yes, there are everyday fats like cooking oils, lard, and heavy cream. These are just the tip of the fat iceberg, as recent science has shown.

The heart attacks Kummerow studied were caused by a specific fat in processed foods, just one of many fatty molecules. But now another deep and enduring mystery has scientists scratching their heads: Why does Nature use thousands of fat molecules, when a small number should suffice?

A new generation of ultrasensitive chemistry technologies has indeed discovered thousands of rapidly shifting fat molecules in the human body that impact nearly all aspects of health. Tracking changes in these fatty molecules predicts future onset of a wide variety of diseases, from heart, brain, and liver diseases to infectious diseases, organ failure, and many cancers, and offers radically new treatment approaches using both diet and drugs.

The heart attack victims had clogged arteries, Fred Kummerow found after examining more than 20 people who died of heart attacks. Trans fats were the culprits — he found vessels clogged with this fat, which is abundant in processed foods. He concluded that thousands of people die from trans fats each year and launched a campaign to ban these fats, which was finally implemented in 2018, 70 years after his first observation.

Many fats hurt your health because they clog your arteries and damage your organs, such as your liver and brain:

  • Trans fats cause deadly heart attacks by blocking blood flow to the heart; they are now illegal due to the work of Kummerow.
  • Cholesterol, a fatty molecule, increases heart attack risk, also by clogging arteries — the commonly used statin drugs work by reducing cholesterol in the body.
  • Saturated fats cause liver damage, brain damage, and heart attacks by clogging arteries and directly damaging these organs.
  • Some fats with complex names reduced to acronyms, such as DGLA, cause brain diseases by killing specific brain cells, such as the ones lost in Parkinson’s Disease, a recent study found

Deadly fats can be categorized based on their chemical structures, and the damage they do. Trans fats, saturated fats, and DGLA have similar pencil-like, long and thin chemical structures, whereas cholesterol looks quite different, more like a series of keyrings strung together. But both kinds of fats are dangerous.

The healthy fats

Healthy hearts and brains require fat molecules with beneficial effects, such as omega-3 fatty acids found in fish. These omega-3 fatty acids have the long pencil-like shape like some of the deadly fats, but with a few kinks, and help the brain and heart function well by dampening an overactive immune system.

Health and longevity are also associated with another fat present in olive oil, which is linked to long life and vitality. In the movie Lorenzo’s Oil, a 5-year-old boy develops a devastating brain disease due to deficiency in healthy fats essential for developing kids.

Oily molecules such as cholesterol and trans fats are called lipids — derived from the Greek word lipos for fat or grease. Unlike most molecules, lipids avoid water and stick in the greasy membranes surrounding cells.

Mapping the world of fatty lipids

DNA and genes are the subject of a vast number of studies. Lipids not so much. Nonetheless, researchers have detected a growing number of lipids in the decades since Kummerow made his discovery about trans fats.

Impressive advances in chemistry detectors have dramatically improved the ability to measure many different lipids in human cells and tissues. Indeed, a single human cell has thousands of distinct lipids, each with a different function and role in health and disease.

A new field of science has sprung up around this technology for detecting lipids, known as lipidomics. Researchers in this new and growing field use sophisticated instruments to measure the amounts of each of thousands of lipids in different cells and different parts of the body.

COVID-19 and other patients with infectious diseases harbor specific lipids. A recent study used lipidomics technology to measure the amounts of thousands of lipids in such patients and found a group of lipids called PEs are elevated in patients with persistent illness; high amounts of PEs predict more severe disease.

PEs are specialized lipids that help form the barrier around cells. Their full formal name is phosphatidyl-ethanol-amines, because they are composed of three pieces—a phosphatidyl group (similar to chemicals in some laundry detergents), an ethanol group (the same molecule found in alcoholic drinks) and an amine, similar to the cleaning product ammonia. When you put these together, you get the PE lipid.

Who will live and who will die? The answer may be found in elevated PEs after infection. This study provided a new way to predict which patients will get better and which will face long-term illness. This information is crucial in determining when and how to treat patients.

This year, Nestor Cortes, a pitcher for the New York Yankees, suffered a rotator cuff injury, which took him out for the season. While we don’t know the details of his specific injury, rotator cuff injuries were associated with elevated PE lipids in a recent study. The rotator cuff consists of muscles around the shoulder joint that keep the arm bone in the shoulder socket. Injury to the rotator cuff causes pain in the shoulder and is common in sports such as baseball. Being able to predict who is likely to suffer this injury could help prevent it, and might have kept the Yankees in contention.

The mystery of lipid complexity and exploding cells

Why so many lipids? Different lipids may control how stretchy and durable cell membranes are. Some membranes are stiffer and others are soft and stretchy. These properties affect how cells interact with each other and how molecules within membranes behave.

Cells can even explode when their lipids react with oxygen. Some lipids, such as the ones that make membrane stretchy, are particularly prone to such reactions. Having too many of these lipids in a membrane can act as a fuse, potentially causing a cell explosion.

The huge untapped resource of lipid biology holds the key to predicting and treating a vast number of diseases. However, the true function of each of the thousands of lipids remains largely unknown, and will require years of study to determine.

Former President Bill Clinton twice had surgery to bypass arteries clogged with fat, after eating fatty fast foods most of life. “I was lucky I didn’t die of a heart attack,” he told Dr. Sanjay Gupta of CNN in 2004. Clinton made a radical switch to a vegan diet, which is low in saturated fat and better for his heart. Best we know, he has been healthy ever since. As Clinton learned, the fats in our diet can indeed be the difference between life and death.

We are on the cusp of a revolution in lipidomic biology driven by this new technology, which continues to advance rapidly. Predicting how lipidomics technology will change healthcare and medicine over the next decade is difficult because the potential is so vast.

We’re using this powerful new technology in my lab at Columbia University to understand which lipids control cell survival, and how we can create new diets and medicines to prevent disease. After all, as computer scientist Alan Kay said, “The best way to predict the future is to invent it.”


Mysterious Fats Fuel Disease More Than We Knew, New Research Reveals was originally published in Wise & Well on Medium, where people are continuing the conversation by highlighting and responding to this story.

17 PUBLICATIONS ON COLUMBIA | ACADEMIC COMMONS

Only select publications listed below
Name Published Date
Identification of essential sites of lipid peroxidation in ferroptosis 2022
Identification of essential sites of lipid peroxidation in ferroptosis (Lipidomics Data) 2022
Klebsiella pneumoniae induces host metabolic stress that promotes tolerance to pulmonary infection 2022
Machine learning classifies ferroptosis and apoptosis cell death modalities with TfR1 immunostaining 2022
Development of therapies for rare genetic disorders of GPX4: roadmap and opportunities 2021
Unsolved mysteries: How does lipid peroxidation cause ferroptosis? 2018
Synchronized renal tubular cell death involves ferroptosis 2014
Modulatory profiling identifies mechanisms of small molecule-induced cell death 2011
Gene expression-based screening for inhibitors of PDGFR signaling 2008
Inhibition of casein kinase 1-epsilon induces cancer-cell-selective, PERIOD2-dependent growth arrest 2008
Identification of Potential Therapeutic Drugs for Huntington's Disease using Caenorhabditis elegans 2007
Inhibitors of metabolism rescue cell death in Huntington's disease models 2007
Identification of inhibitors of ribozyme self-cleavage in mammalian cells via high-throughput screening of chemical libraries 2006
Microarrays of small molecules embedded in biodegradable polymers for use in mammalian cell-based screens 2004
PathBLAST: a tool for alignment of protein interaction networks 2004
Conserved pathways within bacteria and yeast as revealed by global protein network alignment 2003
Systematic discovery of multicomponent therapeutics 2003